Correction of Vitamin D Deficiency Linked to Reduced Low-Grade Chronic Inflammation

by | Oct 12, 2022 | Vitamin D - General

Written by Taylor Woosley, Staff Writer. Study analysis of 294970 subjects who participated in the UK Biobank shows that compared with those with 50 nmol/L, individuals with serum 25(OH)D concentration at 25 nmol/L have a 6.4% (95% CI, 3.85-8.98) higher serum CRP concentration. 

vitamin D capsulesAcute inflammation is a normal part of the immune response; an essential coordination of antibodies and immune cells at sites of infection or injury1. However, growing evidence suggests chronic low-level elevation of proinflammatory cytokines contributes to age-related decline in function2. C-reactive protein (CRP) is a major acute-phase reactant and a sensitive biomarker of chronic low-grade inflammation that has been viewed as a risk factor for a variety of diseases3.

Vitamin D (25(OH)D), a lipid-soluble vitamin, plays an essential role in immune system regulation among other health benefits4. Vitamin D deficiency is prevalent globally and the Endocrine Society defines deficiency as levels less than 20 ng/mL (50 nmol/L) and insufficiency as levels 21-29 ng/mL (52 to 72 nmol/L)5. Adequate levels are needed to allow for immune modulatory mechanisms which can decrease a pro-inflammatory environment6. Vitamin D appears to function as a negative-feedback regulator, attenuating the inflammatory immune responses7.

Zhou et al. conducted a study to assess evidence for the causality of the association between 25(OH)D and CRP levels using a linear and non-linear Mendelian randomization (MR) approach. Data used in the study was obtained from the UK Biobank, a large prospective cohort study with >500,000 participants (aged 37-73 years) gathered between 2006-2009. Subjects completed questionnaires on broad health and lifestyle information, along with providing blood samples for biomarker and genetic assays.

Final analyses were conducted among participants with information on serum 25(OH)D and CRP levels (n=294970). VitaminD-GS, a weighted genetic score consisting of 35 single-nucleotide polymorphisms (SNPs), was utilized to evaluate serum 25(OH)D concentration. An alternative instrument, vitamin-GS-122, was included as a sensitivity analysis. The genetic score for serum CRP concentration, CRP-gwasGS, was analyzed using 46 genome-wide significant variants associated with serum CRP concentration. An alternative instrument using four cis-acting variants was constructed as a sensitivity analysis. Linear and non-linear MR analyses were performed to evaluate the genetic evidence for the bidirectional association between serum 25(OH)D and CRP concentrations. If a non-linear association was present, further stratified MR analyses were performed as a sensitivity analysis. The genetic score-based approach was utilized to calculate MR estimates of the linear, non-linear and stratified MR analyses. Significant findings of the study are as follows:

  • Serum 25(OH)D and CRP concentrations are inversely related in a dose-dependent manner (P < 1.0E-300).
  • Vitamin D-GS was strongly associated with serum 25(OH)D concentration in subjects, explaining 2.8% of variation (F-statistic=8646, P < 1.0E-300).
  • CRP-gwasGS accounted for 6.0% of variation in the serum log RP concentration with a F-statistic of 18687 (P < 1.0E-300).
  • There was evidence of heterogeneity in the CRP-gwasGS-CRP association across 100 strata of residuals of serum CRP, with the 1st and 100th strata appearing to be the outliers PCochran’s Q= 2.66E-13, Ptrend=0.28).
  • A genetic association of serum 25(OH)D with CRP concentration was observed only among individuals with residual 25(OH)D<25 nmol/L, where each 10-nmol/L higher serum 25(OH)D concentration was associated with 7.70% lower CRP (95% CI, -10.9, -4.34, P=1.1E-05).

Results of this large-scale genetic analysis shows evidence for a casual effect of vitamin D status on CRP with no support for CRP as a determinant of 25(OH)D concentrations. The association was largely restricted to subjects with lower serum 25(OH)D concentrations. Correction of vitamin D deficiency is likely to reduce chronic low-grade inflammation in individuals. Study limitations include the use of only CRP as an inflammatory biomarker which does not capture the complexity of the immune system and the lack of population diversity which is not representative of the general public in the UK.

Source: Zhou, Ang, and Elina Hyppönen. “Vitamin D deficiency and C-reactive protein: a bidirectional Mendelian randomization study.” International Journal of Epidemiology (2022).

© The Author(s) 2022. Published by Oxford University Press on behalf of the International Epidemiological Association. 1 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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Posted October 12, 2022.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

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